Tumor heterogeneity as well as the occult nature of MRD often lead to failure in detection when only a single method is used; thus, optimal MRD surveillance should utilize multiple independent techniques, such as the inclusion of both immunologic and molecular based assays, as well as serial samplings over time. However, time, cost, and quality-control issues need to be considered. Potential NB targets identified by gene expression arrays will likely enhance detection sensitivity and specificity. The NB research thus far has implicated that, among selected groups of stage-4 NB patients, the presence of minimal residual tumor cells in the BM and PB at specific phases of the multi-modality treatment scheme is likely to portend an adverse survival outcome; however, to fully understand the role of MRD in the overall management of high-risk NB, a large multi-center prospective study with uniformly treated patients using quality-controlled detection techniques is warranted.
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